New Results on a Promising PD Treatment: GDNF Therapy

Recently, results have been published in the journals of Brain and The Journal of Parkinson’s Disease from a clinical trial studying Glial Cell Line Derived Neurotrophic Factor (GDNF) as a treatment option for Parkinson's disease (PD).1,2 GDNF is a growth factor that may help stimulate the regeneration of cells that have been damaged as a result of PD, potentially improving symptoms and even possibly reversing disease progression. GDNF cannot cross the blood-brain barrier, and therefore, needs to be administered directly to the brain rather than given as a medication. While some studies have looked at GDNF’s impact on PD progression and symptoms, this is the first study in which GDNF was delivered directly to a specific area in the brain using a surgically implanted device rather than other, less-invasive methods.

Study methods

The device, called a convection-enhanced delivery system (CDS), was implanted in 41 individuals with PD using robot-assisted surgery, which involved inserting four tubes into the brain in order to reach an area called the putamen. Brain cells that have been impacted by PD may be found in the putamen and have been predicted to respond to GDNF. The safety of the CDS device and GDNF were assessed in the first six individuals involved in the trial. All participants had a CDS placed, but not all received GDNF, in order to look for any differences in side-effects between those receiving the therapy and those who didn’t. This part of the study found that the CDS and GDNF were safe to use. The next 35 participants followed a similar pattern, with all getting a CDS implanted, but only about half receiving the GDNF. Those who didn’t receive GDNF were given a placebo (a non-medically active substance) through their CDS. Both the GDNF and placebo groups were given an infusion every four weeks for nine months total.

Results of the study

All individuals were between 35 and 75 years old, and had moderate PD severity in the OFF state at the start of the trial. Interestingly, there weren’t any clinically significant changes between the placebo- and GDNF-receiving groups at the end of the study, meaning that the study’s primary endpoints, including symptom reduction, were not met. However, all participants were given a PET scan of their brain, and these results were incredibly significant. Those who received a placebo had no change in their brain scan between the start of the study and the end. On the other hand, those who received GDNF had a 100% improvement in the part of the putamen targeted by the CDS device, showing that regeneration of damaged cells in the brain may be possible with GDNF.

What does this mean for people with Parkinson's?

The researchers predicted that the physical results of GDNF, such as symptom reduction, may not have been seen yet, and may lag behind the changes in the brain. For example, if it took nine months for the participants to experience improvement in their brain, it may take longer than nine months to see any outward changes from this, which the initial portion of the study didn’t measure. In order to further investigate this, the researchers allowed all participants to receive GDNF for an additional nine months after the study was completed (regardless of whether or not they received GDNF or placebo in the first place). During this follow-up period, a large overall improvement in PD symptoms was found across all individuals, suggesting that a longer dosing period may help uncover further benefits of GDNF therapy. However, since everyone received GDNF during this period, there was no control (or placebo) group to compare to, so these results need to be further investigated and strengthened.

The trial and development of the CDS was supported by The Cure Parkinson’s Trust (CPT), Parkinson’s UK, and North Bristol NS Trust. Further studies looking at GDNF and other similar compounds are currently underway, and involve using the CDS and gene therapy (treatments that are focused on impacting an individual at the level of their DNA rather than via a medication) in an effort to better understand the optimal dosing amount and length of time for these treatment options. Results from these studies should be available in the coming years.3,4 The BBC broadcasting network in the United Kingdom has also made a short television series on the CDS and GDNF as well.5

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